entecavir Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
antivirals carbocyclic nucleosides 1019 142217-69-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • entecavir monohydrate
  • anhydrous entecavir
  • BMS-200475-01
  • entecavir
  • baraclude
  • entecavir hydrate
Entecavir, a guanosine nucleoside analogue with activity against HBV reverse transcriptase, is efficiently phosphorylated to the active triphosphate form, which has an intracellular half-life of 15 hours. By competing with the natural substrate deoxyguanosine triphosphate, entecavir triphosphate functionally inhibits all three activities of the HBV reverse transcriptase: (1) base priming, (2) reverse transcription of the negative strand from the pregenomic messenger RNA, and (3) synthesis of the positive strand of HBV DNA. Entecavir triphosphate is a weak inhibitor of cellular DNA polymerases alpha, beta, and delta and mitochondrial DNA polymerase gamma with Ki values ranging from 18 to > 160 microM.
  • Molecular weight: 277.28
  • Formula: C12H15N5O3
  • CLOGP: -2.58
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 4
  • TPSA: 125.76
  • ALOGS: -1.63
  • ROTB: 2

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.50 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 2.40 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 70 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.05 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 99 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

DateAgencyCompanyOrphan
March 29, 2005 FDA BRISTOL MYERS SQUIBB

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hepatitis B 161.45 21.13 41 3723 3652 46678646
Hepatitis B reactivation 152.06 21.13 33 3731 1481 46680817
Drug resistance 134.08 21.13 51 3713 17317 46664981
Hepatitis B DNULL increased 114.15 21.13 19 3745 195 46682103
Viral load increased 105.25 21.13 24 3740 1351 46680947
Exposure via body fluid 80.01 21.13 16 3748 478 46681820
Hypophosphataemia 65.44 21.13 24 3740 7343 46674955
Hepatocellular carcinoma 60.84 21.13 18 3746 2821 46679477
Abortion induced 54.37 21.13 23 3741 10237 46672061
Hepatic cancer 50.85 21.13 16 3748 3081 46679217
Viral mutation identified 49.40 21.13 14 3750 1885 46680413
Maternal exposure during pregnancy 48.48 21.13 50 3714 102499 46579799
Osteomalacia 42.47 21.13 10 3754 647 46681651
Hepatic failure 40.33 21.13 28 3736 33388 46648910
Fanconi syndrome acquired 38.61 21.13 10 3754 959 46681339
Liver transplant 37.66 21.13 12 3752 2405 46679893
Pathogen resistance 36.88 21.13 15 3749 6045 46676253
Hepatic function abnormal 35.02 21.13 26 3738 34395 46647903
Pregnancy on contraceptive 28.06 21.13 8 3756 1099 46681199
Hepatic encephalopathy 26.59 21.13 14 3750 10143 46672155
Neutrophil count decreased 25.76 21.13 24 3740 43402 46638896
Fanconi syndrome 24.62 21.13 7 3757 953 46681345
Abortion spontaneous 23.75 21.13 23 3741 43623 46638675
Genotype drug resistance test positive 23.49 21.13 6 3758 544 46681754
Viral uveitis 23.15 21.13 4 3760 52 46682246
Platelet count decreased 23.08 21.13 34 3730 99990 46582308
Renal impairment 22.78 21.13 29 3735 74343 46607955
Febrile neutropenia 21.59 21.13 32 3732 94595 46587703
Leukopenia 21.48 21.13 27 3737 68316 46613982
Gastroenteritis staphylococcal 21.26 21.13 4 3760 86 46682212

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hepatitis B 343.54 16.88 107 7896 5965 29938510
Drug resistance 312.99 16.88 137 7866 19996 29924479
Hepatic cancer 266.88 16.88 90 7913 6458 29938017
Hepatocellular carcinoma 265.71 16.88 99 7904 9511 29934964
Genotype drug resistance test 182.51 16.88 29 7974 45 29944430
Hepatic failure 181.48 16.88 113 7890 33930 29910545
Hepatitis B DNULL increased 163.80 16.88 36 7967 491 29943984
Viral mutation identified 159.91 16.88 49 7954 2577 29941898
Hepatitis B reactivation 155.50 16.88 49 7954 2828 29941647
Osteomalacia 110.02 16.88 29 7974 879 29943596
Viral load increased 103.61 16.88 36 7967 2818 29941657
Hypophosphataemia 99.16 16.88 47 7956 8198 29936277
Fanconi syndrome acquired 97.97 16.88 32 7971 2071 29942404
Ascites 95.32 16.88 78 7925 35843 29908632
Hepatic cirrhosis 92.51 16.88 56 7947 15943 29928532
Blood HIV RNULL decreased 86.74 16.88 12 7991 0 29944475
Hepatic encephalopathy 85.48 16.88 51 7952 14141 29930334
Hepatic function abnormal 69.66 16.88 70 7933 41875 29902600
Pathogen resistance 55.30 16.88 32 7971 8378 29936097
Viral infection 53.39 16.88 39 7964 15146 29929329
Hepatitis B surface antigen positive 52.55 16.88 11 7992 117 29944358
Osteoporosis 50.74 16.88 33 7970 10630 29933845
Genotype drug resistance test positive 49.89 16.88 18 7985 1571 29942904
Blood phosphorus decreased 48.46 16.88 21 7982 2971 29941504
Portal vein thrombosis 39.36 16.88 19 7984 3445 29941030
Multiple-drug resistance 39.17 16.88 18 7985 2923 29941552
Palmar-plantar erythrodysaesthesia syndrome 38.78 16.88 32 7971 14838 29929637
Fanconi syndrome 37.30 16.88 15 7988 1760 29942715
Autoimmune haemolytic anaemia 33.67 16.88 18 7985 4041 29940434
Renal impairment 33.25 16.88 71 7932 84113 29860362
Renal tubular injury 31.02 16.88 10 7993 620 29943855
Alanine aminotransferase increased 30.91 16.88 64 7939 74212 29870263
Mycoplasma infection 29.26 16.88 8 7995 279 29944196
Hypocalciuria 28.91 16.88 4 7999 0 29944475
Portal vein occlusion 27.42 16.88 6 7997 80 29944395
Parotid gland haemorrhage 27.19 16.88 5 7998 25 29944450
Asymptomatic viral hepatitis 26.71 16.88 5 7998 28 29944447
Retinopathy hypertensive 24.90 16.88 7 7996 271 29944204
Liver transplant 24.87 16.88 13 7990 2789 29941686
Blood bilirubin increased 24.75 16.88 39 7964 36597 29907878
Hepatitis B e antigen positive 23.90 16.88 5 7998 53 29944422
Renal tubular acidosis 23.79 16.88 11 7992 1811 29942664
Foetal heart rate abnormal 23.01 16.88 6 7997 174 29944301
Foetal hypokinesia 22.79 16.88 7 7996 370 29944105
Retinal toxicity 22.40 16.88 7 7996 392 29944083
Liver transplant rejection 21.83 16.88 11 7992 2187 29942288
Blood uric acid 21.68 16.88 3 8000 0 29944475
Renal glycosuria 21.28 16.88 4 7999 23 29944452
Blood creatine phosphokinase increased 20.88 16.88 40 7963 43808 29900667
Haemorrhagic cholecystitis 20.48 16.88 4 7999 29 29944446
Aspartate aminotransferase increased 20.04 16.88 49 7954 63373 29881102
Jaundice 19.79 16.88 33 7970 32453 29912022
Alkalosis hypokalaemic 19.61 16.88 3 8000 3 29944472
Antiviral drug level below therapeutic 19.61 16.88 3 8000 3 29944472
Laryngeal erythema 18.39 16.88 3 8000 6 29944469
Amylase increased 18.29 16.88 14 7989 5827 29938648
Schistosomiasis 17.96 16.88 4 7999 58 29944417
Hepatitis B antigen positive 17.53 16.88 3 8000 9 29944466
Cancer surgery 17.44 16.88 6 7997 455 29944020
Neonatal respiratory distress 17.35 16.88 6 7997 462 29944013
Transaminases increased 17.28 16.88 26 7977 23431 29921044
Lipase increased 17.24 16.88 16 7987 8660 29935815
Dyspnoea 17.19 16.88 40 7963 333255 29611220
Hepatectomy 17.10 16.88 4 7999 73 29944402
Hepatitis B virus test positive 17.08 16.88 5 7998 224 29944251
Completed suicide 17.07 16.88 3 8000 99489 29844986
Varices oesophageal 17.03 16.88 11 7992 3498 29940977

Pharmacologic Action:

SourceCodeDescription
ATC J05AF10 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Nucleoside and nucleotide reverse transcriptase inhibitors
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000998 Antiviral Agents
CHEBI has role CHEBI:36044 anti-virus drug
CHEBI has role CHEBI:59897 rna-dependent dna polymerase inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Chronic type B viral hepatitis indication 61977001
Lamivudine-Refractory Chronic Hepatitis B indication
Lactic acidosis contraindication 91273001 DOID:3650
Liver function tests abnormal contraindication 166603001
Steatosis of liver contraindication 197321007
Impaired renal function disorder contraindication 197663003
Drug Resistance to Anti-retroviral Therapy contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.56 acidic
pKa2 12.33 acidic
pKa3 13.37 acidic
pKa4 4.58 Basic
pKa5 3.37 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Protein P Polyprotein INHIBITOR CHEMBL CHEMBL
Protein P Polyprotein WOMBAT-PK

External reference:

IDSource
4024911 VUID
N0000171606 NUI
D04008 KEGG_DRUG
209216-23-9 SECONDARY_CAS_RN
4024911 VANDF
C2699999 UMLSCUI
CHEBI:473990 CHEBI
CHEMBL713 ChEMBL_ID
DB00442 DRUGBANK_ID
135398508 PUBCHEM_CID
C413685 MESH_SUPPLEMENTAL_RECORD_UI
5968Y6H45M UNII
1546027 RXNORM
19722 MMSL
228280 MMSL
67562 MMSL
d05525 MMSL
010730 NDDF
416248007 SNOMEDCT_US
416644000 SNOMEDCT_US
725853008 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
BARACLUDE HUMAN PRESCRIPTION DRUG LABEL 1 0003-1611 TABLET, FILM COATED 0.50 mg ORAL NDA 28 sections
BARACLUDE HUMAN PRESCRIPTION DRUG LABEL 1 0003-1612 TABLET, FILM COATED 1 mg ORAL NDA 28 sections
BARACLUDE HUMAN PRESCRIPTION DRUG LABEL 1 0003-1614 SOLUTION 0.05 mg ORAL NDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 10135-615 TABLET, FILM COATED 0.50 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 10135-616 TABLET, FILM COATED 1 mg ORAL ANDA 29 sections
ENTECAVIR HUMAN PRESCRIPTION DRUG LABEL 1 16714-717 TABLET, FILM COATED 0.50 mg ORAL ANDA 27 sections
ENTECAVIR HUMAN PRESCRIPTION DRUG LABEL 1 16714-718 TABLET, FILM COATED 1 mg ORAL ANDA 27 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 16729-388 TABLET, FILM COATED 0.50 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 16729-389 TABLET, FILM COATED 1 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 42291-261 TABLET, FILM COATED 0.50 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 42291-262 TABLET, FILM COATED 1 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 42806-658 TABLET 0.50 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 42806-659 TABLET 1 mg ORAL ANDA 28 sections
ENTECAVIR HUMAN PRESCRIPTION DRUG LABEL 1 48792-7891 TABLET, FILM COATED 0.50 mg ORAL ANDA 28 sections
ENTECAVIR HUMAN PRESCRIPTION DRUG LABEL 1 48792-7892 TABLET, FILM COATED 1 mg ORAL ANDA 28 sections
ENTECAVIR HUMAN PRESCRIPTION DRUG LABEL 1 50771-013 TABLET, FILM COATED 0.50 mg ORAL ANDA 28 sections
ENTECAVIR HUMAN PRESCRIPTION DRUG LABEL 1 50771-014 TABLET, FILM COATED 1 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 51407-064 TABLET, FILM COATED 0.50 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 51407-065 TABLET, FILM COATED 1 mg ORAL ANDA 29 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 51991-895 TABLET 0.50 mg ORAL ANDA 31 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 51991-896 TABLET 1 mg ORAL ANDA 31 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 60050-057 TABLET 0.50 mg ORAL ANDA 31 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 60050-077 TABLET 1 mg ORAL ANDA 31 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 60687-216 TABLET 0.50 mg ORAL ANDA 26 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 62227-101 TABLET 0.50 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 62227-102 TABLET 1 mg ORAL ANDA 28 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 65162-446 TABLET, FILM COATED 0.50 mg ORAL ANDA 26 sections
Entecavir HUMAN PRESCRIPTION DRUG LABEL 1 65162-449 TABLET, FILM COATED 1 mg ORAL ANDA 26 sections
Entecavir Human Prescription Drug Label 1 65862-841 TABLET 0.50 mg ORAL ANDA 26 sections
Entecavir Human Prescription Drug Label 1 65862-842 TABLET 1 mg ORAL ANDA 26 sections